The primary objective of this project is to develop data to better understand human immune responses to Neisseria gonorrhoeae infections. Closely coupled with this objective is the need to develop improved understanding of the pathogenesis of the mucosal infection and how it leads to invasive disease. Most strains of N. gonorrhoeae show a continuum of isogenic colony phenotypes. We have utilized piliated, heavily piliated, or nonpiliated transparent and opaque colony variants of the organisms. The transparent colony variants appear to be invasive form of N. gonorrhoeae while the opaque variants tend to be found in male urethra and may have advantage for transmission and attachment to mucosal surfaces. The opaque variants tend to have outer membrane proteins not usually found in the transparent variants. In our study, we are examining the antibody-complement-mediated effects on the various colony phenotypes. Also, we are studying the kinetics of attachment and invasion of the N. gonorrhoeae colony phenotypes to cells and tissues of human origin.